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The science is in. The evidence is clear and sufficient. A group of leading health professionals, scientists and advocates agrees that chemical exposures are putting children at risk for neurodevelopmental disorders like autism, ADHD and learning disabilities. EHS Center Director, Irva Hertz-Picciotto is the co-founder of Project TENDR, an organization that is working to protect infants and children from preventable threats to healthy brain development. Watch the new documentary about Project TENDR.

Role of Environmental Chemicals in the Pathogenesis of Autoimmune Disease Although it is well known that environmental pollution poses significant health hazards, data on the environment and human autoimmunity are limited. This study will examine the effects of a group of well-defined environmental pollutants on the immune functions of patients with systemic lupus erythematosus (SLE), a classical, systemic autoimmune disease. Data from this work will enhance our understanding on how chemical pollutants contribute to the development of SLE and provide insights on the etiology and clinical management of environmental-triggered autoimmune disease.

Dysregulation of MicroRNAs in Ocular Tissue Exposed to Cigarette Smoke Age-related macular degeneration (AMD), a blinding disease having both genetic and environmental components, is the most common form of visual impairment in elderly individuals of the Western world, and smoking is the leading identified associated environmental insult. Recently, a central regulatory role for a novel type of molecule, microRNA (miRNA), had been discovered in many human diseases. MiRNAs are considered to be master regulatory switches, playing roles in stem cell differentiation, aging, epigenetics, etc. Although knowledge about miRNAs and their functions is rapidly accumulating, their roles in healthy ocular aging vs. age-related pathologies in the eye is lacking. Our long-term goal is to elucidate the regulatory role of miRNAs in the eye during normal aging and disease. The goal of this project is to address how circulatory miRNA populations change during normal eye aging, and how that process is accelerated and dysregulated during heightened level of environmental insult such as chronic exposure to cigarette smoke. Our central hypothesis is that normal age-related homeostatic processes whose failure causes/allows the transition from healthy aging to disease are regulated by miRNAs. We will determine which miRNAs show aging-related change of expression using a

Maternal Metabolome, PON1 Status, Organophosphate Exposure and Childhood Autism With the rapid rise in autism spectrum disorder (ASD) diagnoses over the last three decades, identification of the causes and mechanisms of this condition is urgently needed. Building on recent findings that children prenatally exposed to pesticides have an increased risk of an ASD diagnosis, serum from children was previously analyzed. A distinct metabolic pattern was found in children with ASD who were exposed to pesticides in utero that revealed associations with insulin regulation. Given the correlation between insulin resistance and decreased activity of paraoxonase 1 (or PON1, an enzyme involved in detoxification), we hypothesize that exposure to pesticides during pregnancy coupled with reduced maternal PON1 activity is associated with the metabolic health of the mother and the neurological outcome and metabolic health of her child. Most of the evidence about environmental factors in autism provides sparse information about the biologic mechanisms of neurodevelopment. This project seeks to generate preliminary data on perturbations in basic biochemical pathways and reduced PON1 status as a consequence of pesticide exposure, and its association with autism in children.

Postnatal Neuroimmune Integration of Environmental Stresses Over the last 40 years, epidemiological studies have shown a disturbing trend of increasing incidence of allergic asthma in children. A wide range of stressors in the womb or during early life can increase the risk of developing allergic childhood asthma. Given the broad spectrum of stressors, it is likely that numerous systems in the body (i.e., the nervous and immune systems) contribute to the observed increase in allergic childhood asthma. Specialized tissues in the body serve to coordinate immune responses and are required for the development of allergic asthma. These tissues are still developing in the lung during early life and receive signals from various systems that control body functions. We hypothesize that the developing tracheal- and bronchial-associated mediastinal lymph nodes are critical sites where environmental exposures change normal development and set the stage for allergic asthma. The stages of development in humans and other primates is not clear; this study will first examine normal development and the consequences of environmental exposures on immune cells.

Environmental Oxidants and the Aging Male: Sperm Function and Embryo Development Age-dependent accumulation of testicular oxidative insult very likely leads to declining sperm function and fertility, cellular damage to spermatogenic stem cells, inefficiency of sperm production, inefficient mitochondrial metabolism, and mutations in nuclear and mitochondrial DNA. Paternal age has been associated with a number of diseases that have mitochondrial etiologies or components, including autism spectrum disorder, schizophrenia and bipolar disorder. We hypothesize that environmental toxins that cause oxidative insult to the testis contribute to these effects. We propose studies that will utilize a highly relevant model of human reproductive health — the rhesus macaque — that will encompass testicular endocrine health, sperm function and embryo development to assess immediate post-fertilization and developmental landmarks in rhesus embryos. We will expose monkey sperm in vitro with known oxidants and assess sperm function as a necessary first step. With pilot project funding, we propose a comprehensive study to determine specific effects on testicular and gamete health from exposures to environmental toxins, including ozone, forest fire/tobacco smoke and other oxidants.

Gastrointestinal Pathophysiology Following Early Life Environmental Exposure The microbiota-gut-brain axis (MGB axis) is an important pathway for maintaining health and well-being. Disruptions in the axis have been identified in numerous disease states, including inflammatory bowel disease, diabetes and autism spectrum disorder. Early development is an important life stage for normal establishment of the microbiota, development of the gastrointestinal (GI) tract and neurobiological growth and maturation, which together modulate the MGB axis. Exposure to pathophysiological stimuli, for example neurotoxicants, during this important developmental period can have long-term consequences on overall health and well-being. We propose to study GI function following exposure to polychlorinated biphenyls (PCB) during gestation and lactation in mice. We will use samples collected from animals used in ongoing studies funded to examine cognition following developmental exposures. We hypothesize that PCB exposure during early development will lead to GI and microbiota defects. These studies will determine whether environmental exposures to potential neurotoxicants can lead to changes in GI physiology and contribute to long-lasting changes in the MGB axis.

Article by Shivani Kamal 2015 pilot award recipient, Dr. Candace Bever conducted a study examining the presence of chemicals in human breast milk. The chemicals she selected for the project are some found in personal-care products such as toothpaste and liquid hand soap. One particular chemical used in these products is triclosan, an antibacterial agent. Triclosan ends up in a person’s body, including breast milk, through the use of products that contain the chemical. One goal of the study was to understand how the patterns of personal care product use relates to the concentrations measured in the breast milk of nursing women. Although this study involved a small group of women, Dr. Bever and her colleagues are developing an antibody-based chemical detection tool that can be used for much larger population-based studies. By improving chemical detection technology, scientists and public health officials can obtain the information they need to evaluate risk and prevent exposures that could harm young infants and children. Read more about this study at the California Aggie

Investigating the links between chemical exposures and toxicological responses for air pollutants using a novel aerosol mass spectrometry method Atmospheric particulate matter (PM) is an important air pollutant associated with cardiovascular disease and other adverse health outcomes. PM can be composed of complex chemical compounds which vary by region and time of year. The connection between the chemical properties of PM and negative health outcomes is still poorly understood. Consequently, there is a critical need for new analytical techniques that can provide rapid, sensitive, and simultaneous measurements of a wide range of toxic species and chemical classes in PM samples. With support from her EHS Center pilot grant, Dr. Zhang is developing a novel technique to enable measurements of a wide range of compounds in both PM and biological samples to investigate the links between PM exposure and biological responses. Through this work, researchers will be able to identify both the sources and key chemical components of PM that contribute to cardiovascular and other diseases. Results from this work will provide much needed information for understanding the health risks associated with PM.

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